CD100 is a 150-kDa transmembrane protein of the class IV semaphorin subfamily (Delaire et al. (1998) Cell. Mol. Life. Sci. 54:1265-1276; Kumanogoh and Kikutani (2001) Trends Immunol. 22:670-676; Kikutani and Kumanogoh (2003) Nat. Rev. Immunol. 3:159-167). CD100 is expressed at high levels in lymphoid organs, including the spleen, thymus, and lymph nodes, and in non-lymphoid organs, such as the brain, heart, and kidney. In lymphoid organs, CD100 is abundantly expressed on resting T cells but only weakly expressed on resting B cells and antigen-presenting cells (APCs), such as dendritic cells (DCs). Its expression, however, is upregulated in these cells following treatment with various immunological stimuli. The release of soluble CD100 from immune cells is also dependent on cell activation.
The expression patterns of CD100 and its high-affinity receptor, plexin-B1, imply a role in axonal guidance. In Drosophila, plexin-B controls the axonal guidance of certain motor neurons by enhancing Rho signaling (Hu et al. (2001) Neuron 32:39-51). CD100 binding to plexin-B1 results in RhoA activation by regulating PDZ-RhoGEF/LARG, the GEF responsible for CD100-induced growth cone collapse in primary hippocampal neurons (Swiercz et al. (2002) Neuron 35:51-63). In addition, CD100 triggers the invasive growth of epithelial cells, including cell-cell dissociation, anchorage-independent growth, and branching morphogenesis by binding to the plexin-B1-Met complex (Giordano et al. (2002) Nat. Cell Biol. 4:720-724).
As CD100 has been implicated in the development of autoimmune diseases, demyelinating diseases, and certain cancers, compositions which block the activity of CD100 are needed.